Tuberculosis (TB) is caused by Mycobacterium tuberculosis. TB is contagious and spreads through the air. Around two billion people, or one third of the world's population, are estimated to be infected with the bacterium and at risk of developing the disease. About 5% of infected people gets sick with tuberculosis in the first two years after infection. The other 95% develops a latent or ‘sleeping’ infection, which is not contagious, but can still develop into TB later in life. The overall lifetime risk for developing TB following infection is estimated to be approximately 10%.
Pulmonary (lung) tuberculosis is the most common and most infectious form of TB worldwide. However, TB can attack any part of the body. According to the latest data of the World Health Organization (WHO), there were 8.8 million new cases of TB in 2010 (WHO report, 2011). In 2010, around 1.4 million people died from tuberculosis, equaling about 3800 deaths a day and one death every 22 seconds. In 2009 there were nearly 10 million orphan children due to TB deaths. The increased mobility of the world's population, with more people traveling across borders, intensifies the spread of the airborne infectious disease. If not treated, each person with active TB infects on average 10 to 15 people every year.
TB mainly affects young adults in their most productive years. Although poverty-related and mostly affecting developing countries, tuberculosis is prevalent in all continents. Symptoms of tuberculosis include a persistent cough, pain in the chest, coughing up blood or sputum, weakness, weight loss, chills, night sweats and fever.
Currently there is only one vaccine against tuberculosis available worldwide: Bacille Calmette-Guérin (BCG). This vaccine, used since 1921, is administered to over 100 million babies every year and can protect children from severe forms of tuberculosis. However, BCG has little to no efficacy in preventing pulmonary TB in (young) adults, the most common and most infectious form of tuberculosis. Moreover, there are serious safety concerns regarding the use of BCG in HIV infected newborns. The burden of the disease, affecting economies worldwide, is estimated at hundreds of billions of dollars annually.
Vaccines—generally accepted as and proven to be both a very efficient and cost-effective way of preventing infectious diseases—can make the difference. More effective, safe vaccines to improve or replace BCG are urgently needed as tuberculosis keeps taking its toll. Modeling studies show that without new vaccines TB can never be eliminated. New vaccines, together with more accurate diagnostics and more efficient drug therapies, would save tens of millions of lives. Vaccines will also be especially crucial in combating multidrug-resistant tuberculosis (MDR-TB) and extensively drug resistant tuberculosis (XDR-TB), forms of TB that are expensive and extremely difficult or virtually impossible to treat.
Control of Mycobacterial tuberculosis (Mtb) infection depends chiefly on cell-mediated immunity (CMI) response. It is widely accepted that antibacterial T cells exert protective effects by secreting interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) to stimulate bacterially infected macrophages. Mtb hides intracellulary in vacuoles of these phagocytes and escapes degradation by the lysosomal machinery. Upon cognate interaction with antibacterial T cells, however, the resulting stimulation of infected macrophages allows them to kill and degrade their intracellular pathogen. Major Histocompatibility Complex (MHC) class II-restricted CD4+ T cells have long been identified as key players in this process. More recent evidence indicates that MHC class I-restricted CD8+ T cells also play an important role in antibacterial protection.
Novel vaccination strategies should therefore aim at inducing plurifunctional (IFN-γ and TNF-α co-producing) CD4+ and CD8+ T cell responses of high magnitude. Very significant differences exist between different vector platforms, and it remains unpredictable which viral vectors can optimally fulfill these requirements.